CN101553195B

CN101553195B - Treatment of meibomian glands

Info

Publication number: CN101553195B
Application number: CN2007800392538A
Authority: CN
Inventors: D·R·科尔布; T·R·威利斯; S·M·格雷农
Original assignee: Kolis Scientific Inc
Current assignee: TearScience Inc
Priority date: 2007-01-09
Filing date: 2007-01-09
Publication date: 2012-05-30
Anticipated expiration: 2027-01-09
Also published as: EP2101697A1; WO2008085162A1; CN101553195A; JP2010515481A; EP2101697A4

Abstract

In one embodiment consistent with the present invention a method of treating mammalian meibomian glands (10) involves clearing the glands by applying a regulated heat (104) to an eyelid containing themeibomian glands to a temperature adequate to melt obstructions in the meibomian glands to put the obstructions in a fluid or suspension (melted) state and maintaining the heat for a time period adeq uate to melt the obstructions. The glands can then be mechanically treated to express fluid from the glands (108), wherein the treating is carried out either during the time period or after the time period but while the obstruction remains in a fluid state. Subsequent pharmacological treatment of the glands by use a pharmacological agent (topical or systemic) (112) can then be used to assist in maintaining proper flow of lipids from the glands. This abstract is not to be considered limiting, since other embodiments may deviate from the features described in this abstract.

Description

The therapy equipment of tarsal glands

The mutual reference of pertinent literature

The application is that Korb etc. submits, is entitled as the Patent Application No. 11/434 of " method and apparatus of treatment meibomian gland dysfunction " on May 15th, 2006; 054 part continuation application; The U.S. Provisional Application that last application requires to submit on July 18th, 2005 number 60/700; 233 priority; The application still be that Grenon etc. submitted on May 15th, 2006, be entitled as the part continuation application of the Patent Application No. 11/434,033 of " method and apparatus that uses the medium treatment gland dysfunction of heating ", and be Patent Application No. 11/434 that submit on May 15th, 2006, that be entitled as " method and apparatus of treatment gland dysfunction " such as Korb; 446 continuation-in-part application, wherein each piece full text is incorporated into this paper by reference.

Copyright statement

The disclosed part of this patent file comprises the material that receives copyright protection.The copyright owner has no objection to patent document or the disclosed true copy (facsimile reproduction) of imitating of patent, because as if in patent and trademark office's patent file or record, but other outer all rights of All rights are reserved.

Invention field

The present invention relates generally to the treatment of mammal eye.More specifically, the present invention relates to through use heating to melt some obturator (or melted join forms material of the solids of obturator) in case, mechanism makes the multiple combination that heals with medicine treat obstruction of tarsal glands with cleaning obturator and obturator during by cleaning.

Background of invention

Human body contains many bodies of gland, comprises lachrymal gland and the sebaceous gland of tarsal glands, face and oxter or the mammary gland in hair-sebum hair gland and the breast of eye.Because age, stimulation, environmental aspect, cell debris, inflammation, hormone imbalances and other, dysfunction can take place in these bodies of gland.A common disease state of eyelid body of gland is because the fluid that obturator causes flows out the limited or interruption of body of gland naturally.

In people's eye, the tear film that covers the eye table is formed by three layers.The rete malpighii that the innermost layer that contacts with the eye table is made up of many mucin.Forming the most intermediate layer of tear film is water layer, and thin (less than 250nm) layer that outermost layer is made up of the lipid of many being known as " eyelid fat (meibum) " or " sebum ".Sebum is flowed to the hole of margo palpebrae through specially making lipid secretions, thereby is formed the lipid layer of tear film by specialized sebaceous gland-type body of gland (therefore, use " sebum " to describe and should secrete) tarsal glands secretion of the expansion that is arranged in palpebra inferior.Typical upper eyelid has about 25 tarsal glandss, and palpebra inferior has than is positioned at big slightly about 20 tarsal glandss of the tarsal glands in upper eyelid.Tarsal glands comprises the multiple capsule appearance acinus that secretions is flowed into the main central canal of body of gland.Make then secretions through by infer the smooth muscle tissue that in discharging sebum, helps out and Li Ao Lang Shi (Riolan) flesh around the hole.Meibomian gland orifices open in the eyelid that is called mucocutaneous connection of margo palpebrae in the junction of mucosa and external skin and on every side.

Particularly, like what in above patent application, set forth, each tarsal glands has straight long central canal, its on side opposite by four layers of epithelial layer lining.Along the length of central canal, a plurality of laterally projecting cystic structures that are called acinus are arranged, produce the glandular secretion thing here.The liner of each acinus is different with main central canal, and wherein these special cells provide the secretions of tarsal glands.Secretions flow to pipeline from each acinus.As if though still indeterminately confirm, exist valve system to be detained secretions when the needs between each acinus and the central canal, drain into central canal with secretions this moment.The hole that then tarsus secretions is stored in central canal and passes through on each body of gland on the margo palpebrae discharges.Nictation and be considered to open hole so that the main mechanism that secretions discharges from tarsal glands around the squeezing action of Lang Shi difficult to understand (Riolan) flesh in the tarsal glands.

The upwards stage of nictation causes that the upper eyelid is pulled upwardly a slice by the excretory lipid of tarsal glands and to cross other of tear film two-layer, thereby forms the protective coating of one type of restriction lower floor evaporation rate.Thereby, should see that the incorrect amount of defective lipid layer or such lipid can cause the accelerated evaporation of water layer, then causes the symptom that is collectively referred to as " xerophthalmia ", such as itch, calcination, stimulation and drying.

Dry eye states has a lot of causes of disease.The common cause of common dry eye states is that wherein body of gland gets clogged or the inaccessible obstacle that forms, and is commonly referred to " meibomian gland dysfunction " (MGD).As employed at this paper; Term " obturation " and " obstruction "; When they refer to meibomian gland dysfunction; Be defined as the partially or completely obstruction or the obstruction of tarsal glands or its any ingredient, have solid, half-solid or agglomerative secretions of stiff and/or stopper, cause excretory limited or more particularly reduce or stop.Also along with reducing or limited secretion, but because situation tarsal glands sustain damage inaccessible or that block because little yellow indicates possible Infection Status, is damaged by other maybe can, the lipid protecting film of the protectiveness of generation is insufficient like this.

Meibomitis, tarsal glands cause its handicapped inflammation, be accompanied by blepharitis (inflammation of eyelid) usually.Can maybe can there be meibomian gland dysfunction in meibomian gland dysfunction, and have tangible lid inflammation with meibomitis.Meibomian gland dysfunction usually is the result of keratotic obstructions, and it partially or completely blocks the central canal (conduit) of meibomian gland orifices and/or body of gland, or possibly, acinus or acinus valve (supposing their necessary beings) or acinus are connected with central canal.Such obturator makes the secretory function sustain damage of single tarsal glands.More specifically; These keratotic obstructions can comprise antibacterial, sebaceous gland substrate, death and/or the epithelial combination that comes off, and referring to Korb etc., meibomian gland dysfunction and contact lenses do not tolerate (Meibomian GlandDysfunction and Contact Lens Intolerance); Ophthalmology association magazine (Journal of theOptometric Association) the 51st volume; The 3rd phase, (1980), 243-251 page or leaf.When obviously finding meibomitis through eyelid outside inspecting, meibomian gland dysfunction can be not obvious, even also be so during with the inspection of the slit lamp biomicroscope of enlargement ratio, because can there not be outside sign, or outside sign can be small in not being noted.Do not have slight change, epithelial cell that the outside sign of the meibomian gland dysfunction of tangible lid inflammation can be limited to meibomian gland orifices on the aperture undue growth and make the aperture of body of gland diminish (pouting) with condensed material as obturator.In not having the serious meibomian gland dysfunction of tangible lid inflammation, change can be significant, margo palpebrae, the aperture that comprises jagged or waveform shrink back and more significantly undue growth and the aperture of epithelial cell on the aperture diminish.

The hormone that betides menopause changes, and the particularly variation of estrogen level, can cause being thickened by the excretory oiliness secretions of tarsal glands owing to the obstruction of gland orifice.Have, the reduction of estrogen level also can make the fertile condition of staphylococcus strengthen again.This can cause that antibacterial travels to body of gland, thereby causes secreting rate to descend.

When the existence owing to obturator makes secretions from the restricted in flow of tarsal glands, observed cell on the margo palpebrae and covered with gland orifice and therefore also limit sebum flow and make the xerophthalmia condition worse.The factor of other that can cause meibomian gland dysfunction or make that meibomian gland dysfunction worsens comprises the age, the obstacle of twinkling, movablely use computer, contact lenses wearing and tearing and health, make and apply some make up such as injury normal nictation of ground; Or other disease, particularly diabetes.

The state of single tarsal glands can change, from producing the fluidic optimum state of clarifying tarsus; To light or moderate meibomian gland dysfunction, wherein produce emulsus fluid or dense or creamy secretions; Block to overall; The secretions that wherein not can be observed any kind of (is seen Korb etc., " increase behind the treatment meibomian gland dysfunction lipid layer of lacrimal film thickness (Increase in TearFilm Lipid Layer Thickness Following Treatment of Meibomian GlandDysfunction ", lachrymal gland body of gland, tear film and dry eye syndrome (Lacrimal Gland; Tear Film; And Dry Eye Syndromes), the 293-298 page or leaf, D.A.Sullivan writes; Plenum publishing house, New York (1994)).The significant chemical change of tarsal glands secretions produces with meibomian gland dysfunction, thereby the tear film component of natural generation changes, and ophthalmic diseases of " xerophthalmia " takes place to be known as usually successively for it.

When the tear film to be used as single entities and its all each layers all be important, have the meaning of particular importance from the excretory lipid layer of tarsal glands because its function be slow down the evaporation of lower floor and when nictation lubricated eyelid to prevent xerophthalmia.

Thereby, in order to summarize, mammal (like, people) the anti-arresting lacrimation film evaporation of tarsal glands secretion of eyelid and the oil of lubricated eye and eyelid.These bodies of gland can so-called by causing " dry eye syndrome " number of mechanisms become and stop up or inaccessible.Though be not only reason, meibomian gland dysfunction (MGD) is known to be the main cause of dry eye syndrome.This obstacle with among the tarsal glands or certain obstruction on its surface be characteristic, flow to form the lipid layer of tear film from tarsal glands to prevent normal lipid secretions.

Such secretions plays a part anti-arresting lacrimation film evaporation and lubricated eye and eyelid, and therefore, their shortage can cause dry eye syndrome.In the main thoroughfare of the body of gland that can form stenosis or occlusion, or possibly comprise the path from acinus to main pipeline in other position, the obturator of tarsal glands or obturator can be present in or cover the aperture of body of gland.

Set up such theory, promptly the acinus of body of gland can have valve in the junction with the body of gland main thoroughfare.Inventor's reasoning, if the work that these valves exist, they are causing the obstruction that under some situation of the mobile minimizing of acinus or locking, also can become.These obturators or obturator can have multiple composition.

As reaction to aforementioned content; Develop multiple therapeutic modality with treatment xerophthalmia disease, comprised the eye drop that is intended to duplicate and substitute natural tear film, the multiple heater that is intended to stimulate the celliferous medicine of tear and is designed to help to remove obstruction of tarsal glands.Other technology relates to the manual compression body of gland.

Eye drop is designed to press close to duplicate the healthy tear film of natural generation such as Refresh

, Soothe

and Systane board eye drop.Yet their application and administration are nothing but symptomatic treatment rather than to the potential cause of disease.Have, the use of eye drop is generally used for uncertain time span again, thereby, secular use can become trouble and costliness.

Also there is suggestion to use medicament forms; Such as tetracycline treatment meibomian gland dysfunction; And such treatment at the U.S. Patent Publication US2003/011426 that is entitled as " method of treatment meibomian gland disease " of Pflugfelder etc., be entitled as the U.S. Patent number 6 of " method of treatment meibomian gland disease "; 455,583 with the PCT publication No. WO 99/58131 that is entitled as the application of meibomian gland disease " tetracycline treatment " in open.Yet it is clinical effectively general that this treatment is not proved to be, and it can be unnecessary under not having the meibomian gland dysfunction situation that is caused by the body of gland obturator when infecting.Like the U.S. Patent number 6 that is entitled as " local corticosteroid with preservative free is used for the treatment that xerophthalmia, filamentary keratitis and delay tear are removed (or circulation) " at Pflugfelder etc.; Disclosed in 153607, the treatment meibomian gland dysfunction is also proposed in the use of corticosteroid.In addition, as if the symptom of xerophthalmia is treated in the treatment of this proposal, and does not treat the potential cause of disease.Have again; As be entitled as the U.S. Patent number 5,958,912 and U.S. Patent number 6 of " in keratoconjunctivitis, using local androgens of using or the ophtalmic treatments of TGF-β "; 107; Disclosed in 289, to use local androgens of using or androgen analog and also be used to the acute xerophthalmia S&S of treatment in keratoconjunctivitis, these two pieces of patents all are issued to Sullivan.

Most of knowledgeable doctors agree that heating is useful in treatment MGD.According to the characteristic of obturator, in fact heating makes the clogged material fusing or is loosening, allows body of gland more freely to begin to produce and drain in lipid and other fluid, thereby can be useful.

A kind of form that is used for the thermal therapeutical of meibomian gland dysfunction is disclosed in the european patent application sequence number PCT/GB2003/004782 that is entitled as " being used for the thermoregulator eyelid that comprises chemical method ".As disclosed in this patent application, a kind of wiper is provided, wherein before use, activation will make said wiper be heated to about 32 ℃-Yue 40 ℃ chemical reagent.Wiper with heat is applied on the eyelid then, can use manual compression to remove the obturator of pipeline then.This method does not have its shortcoming, but the stimulation of wherein nonspecific temperature eyelid increases the weight of.

Make another method of eyelid and tarsal glands heating be to use near infrared ray (NIR).More particularly, the interpupillary distance according to the curee is attached to two hard eye pasters on the eyeshield.Through the elasticity headband eyeshield being fixed goes up in position.Each paster uses 19 emission 850nm-1050nm, and peak value is the light emitting diode of the near infrared ray of 940nm.This device produces 10mW/cm after energising ²Energy.Goto; E. etc., through the treatment of infrared hot compress (InfraredWarm Compression) device to non-inflammation obstructive meibomian gland dysfunction, Britain's ophthalmology magazine (British Journal of Ophthalmology); The 86th volume (2002), the 1403-1407 page or leaf.This device is designed to use the untouchable Infrared Heating eyeshield of IR light emitting diode.Yet, use IR heating mechanism to have many potential problems.For example, the penetrable eyelid of IR heat gets into cornea, and this is undesirable, and can finally cause cataract or other damage.Have again, determined eyelid not to be applied any pressure (though being described to pressue device) getting rid of the useful IR eyeshield heater of obstruction.In addition, the test that this eyeshield sample is implemented discloses, although be potentially dangerous, this eyeshield produces actual temperature hardly.

The U.S. Patent Publication US2004/0237969 that is entitled as " therapeutic eyeshield and eyelid cover " has been contained a pair of be suitable for to eyelid makes the protective eye lens of body of gland heating more particularly to tarsal glands released heat saturated air.Thermal therapeutical to eye also is being published in by Mitra etc. Ophthalmology, discuss in the article of being entitled as in (2004) the 1-4 pages or leaves " lipid layer of lacrimal film thickness and eyes comfort level after normal curee treats tarsus via the latent heat of new device ".

The U.S. Patent Publication US2003/0233135 that is entitled as " method and apparatus that is used to prevent and treat eyelid disease " of Yee attempt to adopt electricity irritation the present invention supposition to quicken the tarsal glands secretion helpful in the inaccessible tarsal glands of method cleaning of Lang Shi difficult to understand (Riolan) flesh.

The summary of some embodiment

A purpose of some embodiment that conforms to the present invention is that the method for treatment mammal eyelid is provided.

Another purpose of some embodiment that conforms to the present invention is; Therapeutic Method is provided; Said method at first causes the tarsal glands of lipid eyelid above and/or under simple eye or the eyes to flow; Can be present in the tarsal glands or the obturator of some type around it to help to remove, assist to keep the mobile of lipid or otherwise assist to promote the lubricated of eye through Drug therapy subsequently.

In an embodiment that conforms to the present invention; The method of treatment mammal tarsal glands comprises the temperature that extremely enough melts the obturator in the tarsal glands through the temperature of regulating through the eyelid that comprises tarsal glands is applied; Thereby make obturator be in fluid or suspension (fusing) state; And keep this temperature a period of time enough to make the obturator fusing and to make obturator be in fluid or suspension (fusing) state, with the cleaning body of gland.Can carry out mechanical treatment so that fluid is extruded body of gland to body of gland then, wherein said processing is during the said time period or after the said time period, but obturator still was in and carried out under fluid or the suspension state this moment.In most cases, this should carry out in about 90 seconds after the said time period finishes.Can adopt then through making the follow-up Drug therapy of medicament (local with or whole body with), assist to keep lipid and suitably flow or otherwise assist to promote the lubricated of eye from body of gland to body of gland.

According to some embodiment, the said time can be about 10-60 minute, and about 15 minutes generally for slightly suiting to moderate MGD case.In cases with severe more, it is essential that 30-45 minute treatment can be, and for unusual cases with severe, is up to and surpasses 60 minutes thermal therapeutical to can be needs.These time hypothetical target temperature are that 44-47 degree and preferred 45 degree are Celsius, and perhaps can shorten a little or prolong a little for lower temperature for higher temperature.Temperature range can 37 degrees centigrade with more than.

In certain embodiments; Said mechanical treatment is through apply at least a the carrying out in constant voltage, vibrational energy, mechanical energy, pulse machine stimulation, the extruding eyelid to eyelid; Apply when hot to eyelid at the same time; Or when eyelid applies the vibratility stimulation, apply heat simultaneously, fluid is extruded as the appearance of milking from one or more bodies of gland.

In another embodiment; The method of treating mammal meibomian gland dysfunction (wherein obturator blocks the secretions of at least a portion from the effusive natural generation of body of gland access opening) comprises with the selected persistent period with selected enough the making temperature that at least a portion obturator is softening or liquefy, at the thermal source that applies the most nearby from the body of gland access opening through regulating; When at least a portion in obturator still is in softening or liquefaction, the body of gland access opening is carried out mechanical treatment, so that remove at least a portion in the obturator; Subsequently, with promoting lipid from tarsal glands free-flow or otherwise assist to promote the lubricated Drug therapy mammal of eye.

In another embodiment; The method of treatment mammal meibomian gland dysfunction (wherein obturator blocks the secretions of at least a portion from the effusive natural generation of body of gland access opening) comprises with the selected persistent period with selected makes enough that at least a portion obturator is loosened, decomposed, the temperature of broken, softening or liquefaction, at the thermal source that applies the most nearby from the body of gland access opening through adjusting; Using before the effect of the thermal source regulated is reversed, the body of gland access opening is carried out mechanical treatment, so that remove at least a portion in the obturator; Subsequently, with promoting lipid from tarsal glands free-flow or otherwise assist to promote the lubricated Drug therapy mammal of eye.

Above general introduction is intended to set forth the embodiment as illustration, and the detailed description below it combines will obtain best understanding, and and is not intended to limit the scope or the implication of appending claims.

The summary of figure

With some tissue of set forth implementing and the exemplary of method of target and advantage, can through reference following will obtain best understanding with the bonded detailed description of accompanying drawing, wherein:

Fig. 1 describes the upper and lower eyelid of people that shows tarsal glands.

Fig. 2 is the cutaway view of illustrative tarsal glands 20.

Fig. 3 is the cutaway view of the tarsal glands 20 of the several congested areas of explanation.

Fig. 4 is the figure of the surfaces externally and internally temperature of patient's eyelid when the eyelid outer surface is heated to about 45 degrees centigrade.

Fig. 5 is a flow chart of describing a therapeutic process that conforms to certain embodiments of the invention.

Fig. 6 is a flow chart of describing another therapeutic process that conforms to certain embodiments of the invention.

Detailed Description Of The Invention

Though the present invention allows that embodiment exists with many different forms; But to scheme to show and will present invention is described with detailed specific embodiments at this paper; It should be understood that; Such embodiment the instance that is considered to principle disclosed, and be not intended to the present invention is restricted to the specific embodiments that institute shows and describes.In the following description, same reference number is used for describing identical, the similar or corresponding part of figure of several views.

Term " " or " one is defined as one or more like this paper use.Term " plural number " as this paper uses is defined as two or more.Like the term " another " that this paper uses, being defined as is second or more a plurality of at least.The term that uses like this paper " comprises " and/or " having ", is defined as to comprise (being open language).Like the term " connections " that this paper uses, be defined as and interrelate, although be not directly necessary be not mechanism goes up necessity.Like term " program " or " computer program " that this paper uses, be defined as and be designed for the job sequence that computer system is carried out." program " or " computer program " can comprise subprogram, function, program, the goal approach in executable application program, target enforcement, applet (applet), servlet (servlet), source code, object code, SB/loading dynamic base and/or be designed for other job sequence of carrying out in computer system.

Run through " embodiment ", " some embodiment ", " embodiment " or the similar term mentioned in the presents, refer to combine the described concrete characteristic of said embodiment, structure or characteristics to be included at least one embodiment of the present invention.Thereby, the appearance of such phrase or be present in that this description a plurality of places in the whole text are unnecessary all to be meant same embodiment.And concrete characteristic, structure or characteristics can any suitable mode unrestrictedly make up in one or more embodiments.

The term that uses like this paper " or ", be interpreted as and comprise or mean any one or any combination.Therefore, " A, B or C " means " following any one: A; B; C; A and B; A and C; B and C; A, B and C ".The exception of this definition will only take place when the combination of key element, function, step or action is repelled with certain mode constitutionally each other.

Like above indication, known meibomian gland dysfunction (MGD) be dry eye syndrome main diseases because of.This disorder is with certain obstruction in the tarsal glands, and the normal lipid secretions of overslaugh is characteristic from the hole of flowing through with flowing out body of gland to tear film.The obturator of tarsal glands or obturator can be present in the hole of body of gland, and the main thoroughfare of body of gland maybe possibly be present in other position, comprise can be the main thoroughfare of the body of gland of stenosis or occlusion.Existing theory thinks, the acinus of body of gland can have valve in the junction, main thoroughfare of they and body of gland, and these valves get clogged in some cases and cause mobile minimizing or the obstruction from acinus.These obturators or obturator can have multiple composition.

Now, with reference to figure 1, the position of tarsal glands 10 is presented at respectively on upper eyelid 12 and the palpebra inferior 14.As in above concise and to the point statement, the upper eyelid contains has an appointment 25 tarsal glandss and palpebra inferior contains 20 tarsal glandss of having an appointment, significant difference.As a body of gland 10 in Fig. 2 cross-sectional view showed, each body of gland comprises central canal or passage 18, secretions flows into wherein and flows to from acinus 19 opens hole 20 to margo palpebrae, through flowing like this so that when nictation, secretions is added to the tear film.Should see, according to the be in position of eyelid, the varying in size of body of gland, and hole 20 is narrower than central canal 18.

The obturator composition will be different different because of the cause of disease of its generation.Yet; In present most of cases, observe; Obturator will exist with dead cell, antibacterial, exfoliative cyte and the exfoliative cyte, emulsus fluid, the dense combination condensed or creamy secretions that accumulate in the keratinization clump, or aforesaid any combination exists with solid, semisolid and stiff form.With reference to figure 3, the simplification view to the obstruction of body of gland 10 has as an example been described.In this example, it is typical case's representative of necessity of all obstruction of tarsal glands things anything but, as above explains, has described solid or half-solid or stiff stopper 24, and it entirely shuts the hole 20 of body of gland 10.Junction at an acinus and central canal shows another obturator 26.Like preceding indication, this can be the location point of the valve in the gland structure, but the embodiment that conforms to the present invention should not limited to by the theory of the tarsal glands structure of reality.

Make these bodies of gland return to normal function though proposed some treatment technologies, most of doctors approve that heat is useful in treatment MGD.According to the character of obturator, heat makes clogged material or combines solids with the material fusing that forms obturator or useful in loosening actual, and this makes body of gland begin more freely to produce and drain lipid and other fluid.Though have been found that the thermal treatment method of in this paper background of invention part, describing many shortcomings are arranged, have been found that the heat treatment technics of in above copending application of quoting, describing is effective and useful.In general, these devices produce the temperature (as detecting at its outer surface) through regulating through directly contacting with eyelid to eyelid, reach to be higher than 37 degrees centigrade, more preferably are about 44-47 degree centigrade, and target temperature is 45 degrees centigrade a treatment temperature.Yet, can use to be placed near other device at eyelid place with to the tarsal glands heat supply.

The external skin surface of having observed people's eyelid is than the low about 1-2 of body temperature degree centigrade, and some differences are arranged.Temperature is increased at least 37 degree can begin to more slight MGD case the treatment effect to be provided.Have been found that a preferred range that is used to treat is 44-47 degree centigrade, it is effective and comfortable for the patient that target temperature is 45 degrees centigrade.In certain embodiments, at this moment between during the section or after this finishes, preferably carry out mechanical energy immediately time period and treat with the heating apparatus have more fluid state so that keep obturator.Can adopt any machinery that causes mechanical pressure to carry out mechanical energy treatment, include but not limited to vibrate, extrude, mechanical pulse is exerted pressure, push and other operation makes fluid extrude and/or make the pipeline or the bore expansion of tarsal glands from body of gland.Mechanical energy can be taked any form, applies mechanical pressure to tarsal glands and locking thing or obturator is released body of gland when aiding in obturator by thermal softening.Both made can use much higher temperature (as, 50-55 degree centigrade) (or pulse persistance short time), if particularly eyelid is anaesthetized, in the case, but the short time use the treatment of higher temperature and the patient do not caused permanent damage.Usually, can use higher temperature to be used for shorter time.In addition, used temperature and time should be personalized, and it is based on the order of severity and patient's tolerance degree of disease.Have been found that generally dark than the colour of skin patient of the shallow patient of the colour of skin can tolerate lower temperature, and the dark patient of the colour of skin tends to show the inflammation that fewer conduct receives thermal result.Adjustable regulation treatment time and/or temperature are to solve these difference.More than each temperature refer to the temperature measured in the eyelid appearance.

Also have, in certain embodiments, when treatment begins with lower temperature and along with time in the past during temperature increase, it is more comfortable that the patient feels.Therefore, should attemperation, this adjusting should be intended to actual temperature that the eyelid appearance used by explanation and control and regulate with mode repeatably.For heat was used, its Temperature Distribution can be constant temperature, maybe can have soaring to tiltedly going up, to tiltedly gradually fall down, peak, paddy, can be pulse, or available multiple characteristics adjusting etc., make it to repeatably but should regulate such distribution.Have been found that also attemperation can cause the mean temperature higher than constant temperature, and can be useful in some applications.

Can be with this temperature maintenance treatment cycle (is safe and useful even do not find as yet for some patient) of about 10-60 minute on the treatment temperature.Have been found that; Perhaps during the treatment of such temperature with control or after this, from tarsal glands mechanical presses lipid and other fluid with fusing or that be in suspension state (because with solid bond material fusing together) the basically obturator of cleaning.More than open the applying to eyelid usually of application extruded action and comprised from the such fluid of the device of the fluidic motion of body of gland-at present and cause and block or inaccessible material fusing or suspendible to extrude fluid or suspension or other mechanical stimulus.In some cases, only apply the gentle power that continues and to help extrusion fluid and suspension, and in other cases, can simultaneously or after heating, use mode of vibration immediately to eyelid.Be suitable for the purpose of presents, term " fusing " is interpreted as and comprises that wherein solids keep the state in the fluid liquid that is suspended in.

In certain embodiments; Like this apply the Patent Application No. of submitting on Mays 15th, 2006 such as Korb through the device of the temperature of regulating, be entitled as the method and apparatus that is used to treat meibomian gland dysfunction 11/434 to eyelid; 054 with Patent Application No. 11/434 that submit to, that be entitled as " fusing obstruction of tarsal glands thing " on May 15th, 2006 such as Steve Grenon; Open in 033, these two pieces of documents are incorporated into this paper by reference.In certain embodiments, the utilization of this device has the unit heater of the heating element heater of heat production when applying the signal of telecommunication.In order to realize that heating element heater is heated to specific temperature range, thermoregulator applies the signal of telecommunication to heating element heater.Eyelid interface machinery is connected to eyelid with unit heater and applies the temperature through regulating to be implemented in the specific temperature range to eyelid.

Such device provides through the temperature of regulating to treating temperature.Hot compress of the routine of in above background of invention, describing (hot compresses) and IR heated mechanical device are not provided at the heating of the adjusting control of treatment under the temperature, and poorer than the temperature effect through regulating of using the device in above that quote, the patent application that is incorporated into this paper, described to use.

In disclosed another embodiment of present patent application, provide the apparatus of in check heat to have unit heater at least one eyelid of patient, and this unit heater have: the heating element heater on first and second of the heat production surfaces when applying the signal of telecommunication; The first surface that is connected to heating element heater is to be passed to heat the fin of eyelid from heating element heater; The second surface that is connected to heating element heater is to reduce the insulator of heat from the second surface loss; With the backboard that is connected to insulator.In order to realize that heating element heater is heated to specific temperature range, thermoregulator applies the signal of telecommunication to heating element heater.Provide to be suitable for tying up on patient's head and to hide the protective eye lens of patient's eyelid with eyeglass, the eyeglass place has tapped bore.Thread spindle is connected through the screw thread eyeglass and with unit heater on the backboard, so that can contact with eyelid until realization through contacting in the axle precession hole unit heater being moved into eyelid.

Many variations in these embodiments possibly include, but are not limited to that sense temperature is provided and the pick off of temperature information is provided to thermoregulator.In certain embodiments, eyelid interface machinery comprises for the protective eye lens that adjustably be connected to unit heater of traveling heater unit to realize contacting with eyelid.Can protective eye lens be connected to unit heater adjustably through threaded connection, can adopt the position of action spiral adjustment unit heater like this.In certain embodiments, unit heater has for heat is passed to eyelid from heating element heater and is connected to the fin on the surface of heating element heater.Fin can be, and for example, heat conducting rubber parts, conduction of heat silicon cell, contains at least a in fluidic element of encapsulation and the solid conduction element.Can conduction of heat gel, cream or liquid be placed between fin and the eyelid to strengthen from the conduction of heat of fin to eyelid.

In certain embodiments, in order to reduce from heating unit to not being the heat loss towards the eyelid direction, unit heater can have the insulator that is connected to the heating element heater surface.Heat insulator can be a kind of in the non--conduction of heat foam element in some embodiment, non--conduction of heat rubber element and the non--conduction of heat solid-state components.In order to regulate the heat production of heating element heater, thermoregulator can apply the pulsewidth modulation signal of telecommunication to heating element heater, and the pulsewidth modulation signal of telecommunication can produce under the control of processor controls.

In certain embodiments, in order to regulate the heat production of heating element heater, thermoregulator can with being integrally formed of switch that applies the signal of telecommunication to the heating element heater selectivity.The signal of telecommunication can be electric current and voltage at least a that selectivity under processor controls control puts on heating element heater.In order to match with eyelid, the pliability part that unit heater can have the contact eyelid maybe can have the rigid element that contacts eyelid, and wherein rigid element is formed as the shape that adapts to eyelid, or their combination.Unit heater can have gluing being used for unit heater is directly sticked on the eyelid maybe and can tie up at eyelid through using adhesive tape.

In certain embodiments, the user interface time that allows the user to set up to be used for treating and temperature is at least a.In certain embodiments, vibration takes place to stimulate the secretion from tarsal glands to eyelid in vibration machine, and wherein vibration machine can transmit the mechanical energy with amplitude and frequency to eyelid.

The device of other heat production and/or generation pressure is open in above patent application of quoting, and said patent application is incorporated into this paper by reference.

Therefore, in view of above situation, perhaps behind the thermal therapeutical immediately or during such thermal therapeutical; Can apply mechanical treatment to eyelid, for example, adopt constant force, extruding (as; Through manual extruding or alternate manner), extrude action or vibration, to stimulate from tarsal glands cleaning fluid or suspension.If behind thermal therapeutical, carry out mechanical treatment, should when the clogged material of tarsal glands is in molten state thereafter, carry out immediately.

With reference now to Fig. 4,, one secondary describe when about 45 degrees centigrade constant-heat source is applied to as an example tried the patient time eyelid inner surface and the figure of eyelid outer surface.Should indicatedly be, blood circulation attempts to regulate the temperature of eyelid, and because the application blood flow increase of heat.For this patient, spend about outer surface of eyelid that made in 4 minutes and reach about 45 degrees centigrade, and the eyelid inner surface reached never that this temperature-the chances are because the thermal conditioning mechanism of health in action.Therefore, if use 45 degree constant-heat sources, can spend at least about 4 minutes to make the eyelid temperature stabilization and reach the treatment temperature.Also wanting indicated from this figure is, when from eyelid removal thermal source, temperature very rapidly drops to body temperature.In fact in all cases, this temperature will descend in 2-3 minute, and more commonly, made patient's eyelid temperature decline only need about 30 seconds to 90 seconds.In this example, temperature descends very fast in removing heating back 30 seconds.In this short time, some or whole obturators that has melted can solidify again.Therefore, if must after applying heat, carry out manual extrusion technique, then manual extruding should be caught up with immediately; Or in about 90 seconds, carry out-and shorter be preferred at interval; As, in 30 seconds, in any case or; Carry out the removal of at least a portion in the obturator like this using before the effect of the thermal source regulated is reversed.Can understand from this figure,, then use the technology formerly of hot compress can be invalid basically if manual extruding is not carried out in the extremely short time.In addition, if the dressing cooling is lower than treatment level before manual extruding, then they possibly only provide few benefit to suffering from the painful patient of firm obturator.

Have been found that the problem that great majority are used for the Drug therapy mode of dry eye syndrome is, when disease related to body of gland and blocks, medicine can not exert an influence to MGD.That is, known drug treatment at present can not be removed obstruction the flowing with the permission lipid of tarsal glands simply.And antibiotic therapy, steroid therapy or other medicines therapy can be used for the xerophthalmia due to other reason, have been found that when relating to body of gland and block, they be invalid (temporary remission perhaps is provided at the most).Though many medicines can be useful in the lipid that promotes tarsal glands produces and flows, it is invalid that such lipid produces, and if secretions can not discharge body of gland, can resist its generation.In fact, promote lipid to produce the more polyblepharon plate function difficulty and the inflammation that can cause body of gland.

Other medicines can help lend some impetus to the tear generation or otherwise improve the tear film through promotion and help the lubricating function to eye.If use separately, such treatment can be invalid or only part effectively, yet after the cleaning tarsal glands, use, can make the generation of tear film all the components recover normal or near normally.Therefore, it is suitable that many medicines can be for further increase tear film, in case and tarsal glands when recovering more normal function, can be and be highly profitable.

Therefore, in case through heat and manual process (as, during the treatment or compressing afterwards, vibration, pulse, manual extruding etc.) made the mobile recovery of tarsal glands, can be useful to keep lipid from the body of gland outflow with the treatment of multiple medicine.Therefore, with reference to figure 5, described therapeutic scheme, this scheme starts from 100, after this, uses the temperature of control in 104 to eyelid, such as by on quote and be incorporated into by reference the temperature of describing in the patent application of this paper that multiple apparatus produced.Preferred temperature is higher than 37 degrees centigrade, and preferred temperature scope is about 44-47 degree centigrade, and target is 45 degrees centigrade.Yet the higher Celsius temperature of shorter time will provide the treatment benefit, and possible side effect is not for causing the slight skin burn of lasting damage.Be lower than this temperature range, treatment trends towards less effect or invalid.The temperature that is higher than this scope can cause patient's serious discomfort, injury eyelid and possibly injure eyes.During higher temperature in this scope, the patient can feel some discomfort of this temperature, but treatment time can reduce, and available anesthetis is alleviated said discomfort.Lower temperature in this scope is effectively, but general cost is than long heating cycle.

By rule of thumb, slightly to patient's starting point of moderate MGD, 15 minutes patients generally do not have unsuitable discomfort in relative constant temperature 45 degree for many.According to the order of severity of MGD disease, temperature, used anesthetis and patient's tolerance degree, spendable time range is about 10-60 minute or is even more.In experiment, use surpasses 1 hour time and does not have tangible untoward reaction.

In case thermal therapeutical is accomplished (and/or during thermal therapeutical), can be in 108 mechanical forces that apply with any way of the mechanical system of above-mentioned discussion, when obturator is in molten state, to extrude fluid or suspension from tarsal glands.When use is pushed body of gland, preferably any apparatus heating in extrusion process, using, so that when extruding, apply or assist to keep temperature simultaneously to body of gland.

Though manual extruding body of gland can be painful; And because the variation of hand control and/or operation; Be invasive inconsistent when using separately with the result; Though with because need the doctor to push body of gland, method of this treatment MGD also can be very uncomfortable to the patient, provable should technology be useful as the step in the method for in difficult case, selecting to use.45-50 the body of gland of between upper and lower eyelid, having an appointment, therefore, it is very time-consuming pushing each body of gland, and therefore, is inefficient and be the uncomfortable tolerance that is difficult to the patient as far as the doctor.Yet, indicated as, unite automatic pressurizing unit and cross aperture and the lipid proper flow that flows out body of gland to tear film with enhanced flow to assist the serious body of gland that blocks of further cleaning, can be useful.Behind the thermal therapeutical, if, normally remarkably more effectively and still less cause patient's discomfort and obtain better result from the body of gland extruding secretions that blocks than using separately.As preceding indicating, when using extruding body of gland method, any apparatus that in extrusion process, uses in heating is preferred, so that when extruding, body of gland is applied temperature simultaneously or temperature is kept in assistance.

In 104 and 108; In case flow from tarsal glands cleaning obturator and other foreign substance and recovery lipid; The body of gland inflammation is minimum, cleaning is infected in order to make, prevent further locking, make lipid thin out, promote tear to produce, increase the composition or the promotion lipid free-flow of tear film or strengthen lubricated any other pharmacology's mode of eyes; In 112, any treatment tarsal glands of available multiple medicine (or the part is used or whole body is used).Drug therapy can be carried out or the short time (as, infect or inflammatory disorders with cleaning) or continue to treat (as, as with making lipid thin out, reduce inflammation or treating the medicine of other form of dry eye syndrome).This process finishes 116.

Many medicines have been proposed to be used to treat dry eye syndrome, and wherein any medicament can be effective or more effective in the cleaning tarsal glands on the obturator.More spendable medicines comprise, but are not limited to: antibiotic such as part with or oral tetracycline and the tetracycline of modifying through chemical method, testosterone, local with or oral corticosteroid, local with androgens or androgen analog, Ω 3 fatty acid cpds such as fish oil, Placenta extract (laennec), promote enzyme that lipid produces, the medicine of the generation that stimulates the enzyme that promotes that lipid produces and as increase tarsal glands secretion or the excretory sercretogogue of other tear composition any medicine.Existing report, androgen and androgen analog and TGF-β as sercretogogue secrete with increasing tarsal glands, alternative or promote the generation medicine of any tear composition, and have many other medicines.These chemical compounds are the illustrative of appropriate drug, but this area professional and technical personnel should be realized that, based on considering that the present invention instructed, can use the chemical compound that other has pharmacological action.Also wanting indicated be, in causing the reason of dry eye syndrome, can comprise multiple mode, but only a kind of mode is treated and can not be caused satisfactory solution.Therefore, make to flow and recover normal or make the tear film recover normal near the alternate manner or the multiple mode of a part-disease that heals with medicine that normally can be only solution from the lipid of tarsal glands.Yet when involving significant MG dysfunction, single treatment otherwise is perhaps less satisfactory.

The mutation of above treatment is described in conjunction with Fig. 6; In 130 beginnings, thereafter in 104, as in the Therapeutic Method formerly; Use temperature to eyelid through regulation and control, such as by above quote with the patent application that is incorporated into this paper by reference in the temperature that multiple apparatus produces is described.The preferred range of such temperature is about 44-47 degree centigrade again, and target is 45 degrees centigrade.Have, spendable time range is about 10-60 minute and more again, and this depends on the order of severity, treatment temperature and patient's tolerance degree of disease.

In this embodiment; During thermal therapeutical, in 138, any mechanical system that can above-mentioned discussion; Comprising those quotes and the mechanical system that is incorporated into this paper by reference; When obturator is in liquid or suspension state during using temperature, apply mechanical pressure, to extrude fluid or suspension from tarsal glands.

In 138,, after removing temperature,, can apply other power immediately in 142 according to the reaction of patient to temperature combination mechanical pressure simultaneously.In the case, in extruding or like the applied force of describing temperature being kept, also is preferred.That is, during pushing, used any probe or the heating of other utensil being in liquid or suspension state to help keeping obturator, is preferred.Can manually apply such power, through extruding eyelid in the residual position of suitable obturator, if or available words can adopt the automation method.

In case in 104,138 and 142; From some or all of tarsal glands cleaning obturator and other foreign substance; The body of gland inflammation is minimum in order to make, cleaning is infected, prevents further locking, lipid thinned out, as preceding, in 112; Available multiple medicine (or the part is used or whole body is used), or promote lipid free-flow or or any other pharmacology's mode of alternate manner promotion tear film improvement.As indicated, Drug therapy can be carried out or the short time (as, infect or inflammatory disorders with cleaning) or continue to treat (as, as with making lipid thin out, improve the medicine of tear composition or minimizing inflammation).This process finishes 150.

Above method no matter whether comprise the method for Fig. 5 or Fig. 6, causes or when keeping from tarsal glands suitable mobile like needs, can repeat or exchange is used at interval.For some patients,, can periodically repeat such treatment or its part in order to keep lipid from the flowing of tarsal glands.

Thereby; Some embodiment that foundation conforms to the present invention; The method of treatment mammal tarsal glands comprises that said temperature reaches the temperature of the obturator in enough fusing tarsal glandss and keeps this temperature a period of time enough to make the obturator fusing and to make obturator be in fluid or suspension (fusing) state through the eyelid that comprises tarsal glands being applied through the temperature of regulating with the cleaning body of gland.Can carry out mechanical treatment so that fluid or suspension are extruded body of gland to body of gland then, wherein said mechanical treatment between the said time or after the said time but this moment obturator still be in and carry out under the molten state.This process can be strengthened with the therapy equipment of holding temperature and obstructive material molten state through the power that applies that is used to of heating.Can adopt then through making the follow-up Drug therapy to body of gland of medicament (part is used or whole body is used), suitably flow from body of gland to assist keeping lipid.

According to some embodiment, the said time can be about 10-60 minute, and about 15 minutes generally for slightly suiting to the moderate case.It is about 44-47 degree centigrade that temperature should be higher than 37 degrees centigrade and eyelid hull-skin temperature preferred range, and target is 45 degrees centigrade, has been found that to the patient it is effective and comfortable.In certain embodiments, after heating, as soon as possible, preferably carry out mechanical treatment in second at about 30-90, so obturator will remain in molten state in extrusion process.In other embodiment; Apply temperature at the same time, or when eyelid applies the vibratility stimulation, when applying temperature simultaneously; Through using constant voltage, extruding, extruding at least a fluid or the suspension from one or more body of gland, carry out mechanical treatment as the appearance of milking.Based on considering that the present invention instructed, this area professional and technical personnel will remember many variations and alternate embodiment.

Though described some illustrative embodiment, be apparent that, many alternative, revise, change and variation, for the professional and technical personnel of this area according to before description will become clear.

Claims

1. apparatus of treating the mammal tarsal glands, said tarsal glands has tarsal glands passage and the tarsal glands access opening on said tarsal glands passage, and said apparatus comprises:

Can be from applying device to eyelid through the temperature of regulating through the thermal source of regulating, wherein said device is configured to

From applying the temperature through regulating through the thermal source of regulating to the eyelid that comprises tarsal glands, said temperature reaches the obturator fusing in the tarsal glands passage that enough makes tarsal glands and makes obturator be in the temperature of molten state;

Keep this through temperature a period of time of regulating enough to make the obturator fusing and to make obturator be in molten state; With

In the tarsal glands passage, extrude the fusing obturator through the tarsal glands access opening; By this one or more tarsal glandss are carried out mechanical treatment, wherein said mechanical treatment carries out when the back obturator still remains on molten state during the said obturator of fusing or during said.

2. the apparatus of claim 1, wherein said a period of time is about 10-60 minute.

3. the apparatus of claim 1 wherein saidly is configured to reach at least 37 degrees centigrade temperature through the thermal source of regulating.

4. the apparatus of claim 1 wherein saidly is configured to reach the temperature between about 44 and 47 degrees centigrade through the thermal source of regulating.

5. the apparatus of claim 1, the wherein said temperature that reaches about 45 degrees centigrade of being configured to through the thermal source of regulating.

6. the apparatus of claim 1 after wherein said device also is provided in a time-histories, applies and keeps the temperature through regulating from the thermal source through adjusting, to keep the outflow of fluid from tarsal glands again.

7. the apparatus of claim 1; Wherein said thermal source through adjusting is set at from the body of gland access opening the most nearby; With from applying through the thermal source of regulating through the temperature of regulating one selected period and chosen temperature, so that enough make the softening or liquefaction of at least a portion obturator.

8. the apparatus of claim 1, wherein said device are configured to be enough to make from applying through the thermal source of regulating that at least a portion obturator is loosened, decomposed, the temperature through regulating of broken, softening or liquefaction.

9. the apparatus of claim 1; Wherein said device also is configured to remove applying through the temperature of regulating from eyelid; So that through when obturator still remains on molten state, the obturator of extruding fusing from the tarsal glands access opening of the tarsal glands passage of one or more tarsal glandss comes tarsal glands is carried out mechanical treatment.

10. the apparatus of claim 1, wherein said device also are configured to remove through the applying of the temperature of regulating from eyelid, with to the tarsal glands drug administration.

11. the apparatus of claim 10, wherein said medicine are selected from antibiotic, local with corticosteroid, oral corticosteroid, local with androgen, local with androgen analog, TGF-β, ω 3 chemical compounds.

12. it is local with tetracycline, oral tetracycline that the apparatus of claim 11, wherein said medicine are selected from antibiotic.

13. the apparatus of claim 10, wherein said medicine be selected from the enzyme that promotes lipid to produce, stimulate medicine that the enzyme that promotes lipid to produce produces, as sercretogogue with strengthening the excretory medicine of tarsal glands.

14. the apparatus of claim 10, wherein said medicine are selected from the medicine that substitutes or promote the generation of any tear composition.

15. the apparatus of claim 10, wherein a plurality of said medicines are selected for use.

16. the apparatus of claim 1, it also comprises the machinery that is set up, so that through when obturator still remains on molten state, extrudes the obturator of fusing from the tarsal glands access opening of the tarsal glands passage of one or more tarsal glandss and handles tarsal glands.

17. the apparatus of claim 16; Wherein said machinery also is configured to apply vibratility to eyelid to stimulate; And/or extruding eyelid or apply constant voltage or apply pulsation to eyelid to eyelid and press, so that the obturator of fusing is extruded from the tarsal glands access opening of the tarsal glands passage of the one or more tarsal glandss appearance that looks like to milk.

18. the apparatus of claim 16, wherein said machinery also are set to supply heating to use.

19. the apparatus of claim 16; When wherein said machinery also is provided in obturator and still remains on molten state; Push time-histories of obturator of fusing repeatedly from the tarsal glands access opening of the tarsal glands passage of one or more tarsal glandss, to keep the outflow of liquid from tarsal glands.